Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice

Abstract

Loss of regenerative capacity plays a critical role in age-related autoimmune hepatitis. Evidence implicates SIRT1 and p66shc in cell senescence, apoptosis, oxidative stress, and proliferation. This study investigated the effect of resveratrol on concanavalin A (Con A)-induced hepatitis in aged mice and the roles of SIRT1 and p66shc. Aged mice were administrated resveratrol (30 mg/kg orally) seven times at an interval of 12 h before a single intravenous injection of Con A (20 mg/kg). Results showed that the cytokines, TNF-α, IL-6, IFN-γ, and MCP-1, as well as infiltration of macrophages, neutrophils, and T lymphocytes in liver were dramatically enhanced in the mice given only Con A. The aged mouse livers showed markedly raised oxidative stress and cell apoptosis. This oxidative stress further aggravated regenerative dysfunction as indicated by the decreased levels of Ki67, PCNA, Cyclin D1, and Cdk2. Conversely, these phenomena were attenuated by pretreatment with resveratrol. Moreover, resveratrol suppressed the elevation of p66shc in the liver by reversing Con-A-mediated downregulation of SIRT1. The findings suggest that resveratrol protected against Con A-induced hepatitis in aged mice by attenuating an aberration of immune response and liver regeneration, partially via the mechanism of SIRT1-mediated repression of p66shc expression.

Protective Function of Novel Fungal Immunomodulatory Proteins Fip-lti1 and Fip-lti2 from Lentinus tigrinus in Concanavalin A-Induced Liver Oxidative Injury

“…No effective treatment is available because of a lack of mechanistic understanding of this disease [25]. Con A-induced liver injury is a well-established model to investigate mechanisms of immunity-associated liver diseases [26] and we used this model to elucidate the beneficial functions of Fip-lti1 and Fip-lti2.…”

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

“…In addition, resveratrol showed immunomodulatory properties via reducing bacterial and inflammatory biomarkers in lipopolysaccharides (LPS)-challenged primary Atlantic salmon macrophages [52]. Resveratrol also modulated immunity caused by some toxic materials like concanavalin A (Con A), showing upregulation of SIRT1 and reduction of cytokines such as TNF-α, interferon γ (IFN-γ), IL-6, and monocyte chemoattractant protein-1 (MCP-1) [53]. Interestingly, resveratrol was found to strongly enhance immune activity in immunosuppressive mice, showing a bidirectional regulatory effect on immunity [54].…”

Sex-Dependent Effects on Liver Inflammation and Gut Microbial Dysbiosis After Continuous Developmental Exposure to Trichloroethylene in Autoimmune-Prone Mice

“…Like IL-6 related markers and chemokines/cytokines, KI67 and Cyclin D1 dysregulation is an indicator of many different liver conditions including hepatocellular carcinoma ( Salama et al, 2019 ), nonalcoholic fatty liver disease ( Dey et al, 2019 ), chronic alcohol exposure ( Chavez et al, 2011 ), and liver injury ( Inomata et al, 2018 ). The role of these proteins are not well described in AIH, however; experimentally-induced AIH had altered levels of these proliferation markers ( Huang et al, 2017 ). Together, these results indicate that the liver in females, relative to males, are more responsive to liver injury, and TCE enhances these effects.…”